Gene therapy heals infants with "bubble boy" immune disease

Ten researchers on Wednesday revealed that ten newborns with a rare genetic disorder, called Bubble Boy's Disease, have been cured by gene therapy. The treatment seems to have completely cleared babies of their immune disorder, with no side effects or complications – a result scientists have been seeking for decades through painstaking research and heartbreaking reverses.

A first attempt at using gene therapy to treat severe combined immunodeficiency disease, or SCID, was discontinued in 2003 after the researchers realized that the therapy was giving cancer to children. The treatment unveiled Wednesday does not seem to have such calamitous side effects, and experts hope that it could help improve treatments for other rare genetic diseases such as sickle cell disease.

"It's a game changer," said Jennifer Hemall, a pediatric immunologist at Philadelphia Children's Hospital, who did not participate in the study. "For immunologists who follow this disease, gene therapy has always been a hope for the future. It's exciting to see this wave of treatments become a reality. "

Infants with SCID are born essentially without a functioning immune system. Without treatment, they rarely survive after their first birthday and can be killed by infections as harmless as colds. These children were once isolated in sterile environments, hence the term "bubble boy". Their unusual situation has attracted the attention of the country and has been put forward in movies and television shows.

The survival rate of recent years has skyrocketed with the advent of widespread screening tests and improved procedures to save lives such as bone marrow transplants. But such treatments have come with complications, often leaving children dependent on regular immunoglobulin infusions or forcing their new immune system to attack their own body.

The New Gene Therapy – developed by the St. Jude Children's Research Hospital and the Benioff Children's Hospital of UCSF in San Francisco and published in the New England Journal of Medicine – corrects the DNA genetic abnormality of babies shortly after birth, thereby stimulating their body to generate missing parts of their immune system.

In interviews, the researchers said that they first extracted some blood stem cells of the infant bone marrow. They used a modified virus as a vehicle to deliver the correct copy of a defective gene into the stem cells of these patients. These corrected cells were then reinjected to the patient, where they proliferated and created healthy immune cells.

To avoid accidentally activating carcinogenic genes as previous gene therapies did, researchers incorporated "insulators" into the virus so that neighboring genes would not be affected when the virus inserted into the DNA. In another innovation, the researchers gave their patients a small amount of chemotherapy to remove existing bone marrow cells before re-infusing the treated cells, giving the corrected cells a better chance of getting settled.

The announcement was bitter-sweet for many at the St. Jude Children's Research Hospital. Brian Sorrentino, their team leader and lead author of the paper, spent the last months of his life battling a fatal cancer to complete his work on experimental treatment.

Sorrentino was diagnosed at a young age with Hodgkin lymphoma, said his widow, Suzanne Sorrentino. Because modern treatments did not exist yet, his doctors treated him using radiation that weakened his heart and caused the lung cancer that killed him last November.

"The hair loss, the pain and the agony of the treatment, that's what motivated him to find new treatments for other diseases in children," said his woman during an interview.

Brian Sorrentino holds Gael Jesus Pino Alva, who was the first patient treated with the new gene therapy for SCID. (St. Jude Children's Research Hospital)

Sorrentino has been working with other immunologists on SCID gene therapy since the 1990s, but his work has taken on a new urgency in the last year and a half of his life after the diagnosis of his cancer. Suzanne. When he could no longer get to the hospital, his colleagues from St. Jude began organizing conference calls and settling down at the Sorrentino table. At that time, it was obvious that the experimental procedure had succeeded. Many of their young patients had become toddlers with a completely normal immune system.

"He told me that he thought he was saved in his childhood at Hodgkin because he thought he would have to do something with his life," said Suzanne, her voice trembling as she said. she remembered one of her last conversations with her husband. "With the trial and the kids going so well, he felt that it was a sign that he had realized what he was supposed to accomplish." It was time for him to leave.

In recent years, while newborn SCID screening has become mandatory across the country, experts have found that the disease is more prevalent than previously thought, and that it occurs. in one in 50,000 infants.

There are several forms of SCID. Gene therapy for a variant called ADA-SCIDS is available in Europe. But a cure for the most common form – the X-linked SCID, found only in boys – remained until now elusive.

The disease attracted national attention in the 1970s with the case of David Vetter. Press points chronicles his life as he grew up cocooning in plastic. His story gave birth to John Travolta's 1976 film "The Boy in the Plastic Bubble". And even after Vetter's death, the insulating effects of the disease kept him in the national consciousness. from a Jake Gyllenhaal movie "Bubble Boy".

Until now, the most effective treatment for SCID had been hematopoietic stem cell transplantation from a sibling-compatible donor, but most patients did not have this type of donor. Half-matched and unrelated donors have also been successful in saving lives, but have often resulted in complications.

The first successful gene therapy trial in 2000 by French doctors gave many researchers and patients hope that they could repair the molecular underpinnings of the disease instead of simply treating its symptoms. But when leukemia was detected in some of these patients, she temporarily interrupted gene therapy trials in America and much of the world and sent discouraged researchers looking for answers.

"Leukemia stopped the field for a long time, rightly, because people had to understand what was wrong," said Jordan Orange, a pediatric immunologist at Columbia University, who said: 39; has not participated in the St. Jude study, but has contributed to the development of gene therapy for another immunodeficiency disease called Wiskott-Aldrich. "But that has led us to the point where we are finally starting to see real cures at incurable conditions."

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